The Disposition and Cerebrospinal Fluid Penetration of Morphine and Its Two Major Glucuronidated Metabolites in Adults Undergoing Lumbar Myelogram

Steven Laizure, Joseph H. Miller, Robert C. Stevens, David J. Donahue, Robert E. Laster, Donna Brown

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Abstract

Study Objective. To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine‐6‐glucuronide (M6G) and morphine‐3‐glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). Design. A single‐dose, open‐label pharmacokinetic study. Setting. The Memphis Neurosciences Center at Methodist Hospital. Patients. Twenty patients undergoing a diagnostic lumbar myelogram. Interventions. All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. Measurements and Main Results. Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean ± standard deviation for the half‐life of morphine was 2.8 ± 1.4 hours. The apparent half‐lives of M6G and M3G were 5.7 ± 3.1 and 6.3 ± 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r=‐0.61, p<0.007 and r=‐0.69, p<0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 ± 0.32 hrs, n=19) were 3.1 ± 3.7, 12.5 ±17.6, and 19.6 ±16.1 nmol/L, respectively. Conclusions. Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G. 1993 Pharmacotherapy Publications Inc.

Original languageEnglish (US)
Pages (from-to)471-475
Number of pages5
JournalPharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume13
Issue number5
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Morphine
Cerebrospinal Fluid
Pharmacokinetics
Spinal Puncture
Neurosciences
Half-Life
Analgesics
Publications
Creatinine
Kidney
Drug Therapy
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

The Disposition and Cerebrospinal Fluid Penetration of Morphine and Its Two Major Glucuronidated Metabolites in Adults Undergoing Lumbar Myelogram. / Laizure, Steven; Miller, Joseph H.; Stevens, Robert C.; Donahue, David J.; Laster, Robert E.; Brown, Donna.

In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Vol. 13, No. 5, 01.01.1993, p. 471-475.

Research output: Contribution to journalArticle

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abstract = "Study Objective. To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine‐6‐glucuronide (M6G) and morphine‐3‐glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). Design. A single‐dose, open‐label pharmacokinetic study. Setting. The Memphis Neurosciences Center at Methodist Hospital. Patients. Twenty patients undergoing a diagnostic lumbar myelogram. Interventions. All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. Measurements and Main Results. Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean ± standard deviation for the half‐life of morphine was 2.8 ± 1.4 hours. The apparent half‐lives of M6G and M3G were 5.7 ± 3.1 and 6.3 ± 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r=‐0.61, p<0.007 and r=‐0.69, p<0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 ± 0.32 hrs, n=19) were 3.1 ± 3.7, 12.5 ±17.6, and 19.6 ±16.1 nmol/L, respectively. Conclusions. Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G. 1993 Pharmacotherapy Publications Inc.",
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N2 - Study Objective. To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine‐6‐glucuronide (M6G) and morphine‐3‐glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). Design. A single‐dose, open‐label pharmacokinetic study. Setting. The Memphis Neurosciences Center at Methodist Hospital. Patients. Twenty patients undergoing a diagnostic lumbar myelogram. Interventions. All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. Measurements and Main Results. Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean ± standard deviation for the half‐life of morphine was 2.8 ± 1.4 hours. The apparent half‐lives of M6G and M3G were 5.7 ± 3.1 and 6.3 ± 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r=‐0.61, p<0.007 and r=‐0.69, p<0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 ± 0.32 hrs, n=19) were 3.1 ± 3.7, 12.5 ±17.6, and 19.6 ±16.1 nmol/L, respectively. Conclusions. Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G. 1993 Pharmacotherapy Publications Inc.

AB - Study Objective. To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine‐6‐glucuronide (M6G) and morphine‐3‐glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). Design. A single‐dose, open‐label pharmacokinetic study. Setting. The Memphis Neurosciences Center at Methodist Hospital. Patients. Twenty patients undergoing a diagnostic lumbar myelogram. Interventions. All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. Measurements and Main Results. Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean ± standard deviation for the half‐life of morphine was 2.8 ± 1.4 hours. The apparent half‐lives of M6G and M3G were 5.7 ± 3.1 and 6.3 ± 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r=‐0.61, p<0.007 and r=‐0.69, p<0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 ± 0.32 hrs, n=19) were 3.1 ± 3.7, 12.5 ±17.6, and 19.6 ±16.1 nmol/L, respectively. Conclusions. Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G. 1993 Pharmacotherapy Publications Inc.

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